cGMP signaling, phosphodiesterases and major depressive disorder

Gillian W. Reierson, Shuyu Guo, Claudio Mastronardi, Julio Licinio, Ma Li Wong

Research output: Contribution to journalReview article

33 Citations (Scopus)

Abstract

Deficits in neuroplasticity are hypothesized to underlie the pathophysiology of major depressive disorder (MDD): the effectiveness of antidepressants is thought to be related to the normalization of disrupted synaptic transmission and neurogenesis. The cyclic adenosine monophosphate (cAMP) signaling cascade has received considerable attention for its role in neuroplasticity and MDD. However components of a closely related pathway, the cyclic guanosine monophosphate (cGMP) have been studied with much lower intensity, even though this signaling transduction cascade is also expressed in the brain and the activity of this pathway has been implicated in learning and memory processes. Cyclic GMP acts as a second messenger; it amplifies signals received at postsynaptic receptors and activates downstream effector molecules resulting in gene expression changes and neuronal responses. Phosphodiesterase (PDE) enzymes degrade cGMP into 5'GMP and therefore they are involved in the regulation of intracellular levels of cGMP. Here we review a growing body of evidence suggesting that the cGMP signaling cascade warrants further investigation for its involvement in MDD and antidepressant action.

Original languageEnglish
Pages (from-to)715-727
Number of pages13
JournalCurrent Neuropharmacology
Volume9
Issue number4
DOIs
Publication statusPublished - Dec 2011
Externally publishedYes

Keywords

  • Antidepressants
  • Cyclases
  • Cyclic guanosine monophosphate
  • Major Depression
  • Neurogenesis
  • Neuroplasticity
  • Pharmacology
  • Phophodiesterases

ASJC Scopus subject areas

  • Pharmacology
  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Pharmacology (medical)

Cite this

Reierson, G. W., Guo, S., Mastronardi, C., Licinio, J., & Wong, M. L. (2011). cGMP signaling, phosphodiesterases and major depressive disorder. Current Neuropharmacology, 9(4), 715-727. https://doi.org/10.2174/157015911798376271